Cellular senescence, actin cytoskeleton, cell cycle, P53 and pathways of neurodegeneration were more prominent signaling pathways astrocyte and oligodendrocyte derived ALS.
After using the Venn tool to find the commonalities between the genes for the three groups, 404, 247, 133 high-expression genes was obtained between astrocyte and oligodendrocyte derived ALS, astrocyte derived ALS, and oligodendrocyte derived ALS respectively. These genes were involved in regulation of actin cytoskeleton, steroid hormone biosynthesis, inositol phosphate metabolism, P53 signaling pathway, cell cycle, cellular senescence, glioma, cAMP signaling pathway, protein digestion and absorption, and T cell receptor signaling pathway were observed in high-expression genes (Fig. 2A). Also, 221, 108, and 107 downregulated genes was obtained between astrocyte and oligodendrocyte derived ALS, astrocyte derived ALS, and oligodendrocyte derived ALS respectively. Regulation of lipolysis in adipocytes, insulin signaling pathway, longevity regulating pathway, aldosterone synthesis and secretion, glucagon signaling pathway, HIF-1 signaling pathway, pathways of neurodegeneration, butanoate metabolism, and tight junction observed in downregulated genes (Fig. 2B).
Evaluation of gene ontology between astrocyte and oligodendrocyte derived ALS.
This section further evaluates the astrocyte and oligodendrocyte derived ALS from the previous step and examines their molecular functions and biological processes. Accordingly, insulin-like growth factor receptor binding, hydrolase activity, hydrolyzing N-glycosyl compounds, oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor, retinoic acid receptor binding, FATZ binding, disordered domain specific binding, water transmembrane transporter activity, hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides molecular functions in upregulated genes. Besides, pseudophosphatase activity, 15-hydroxyprostaglandin dehydrogenase (NAD+) activity, Phenanthrene 9,10-monooxygenase activity, Histone deacetylase binding, Transmembrane receptor protein tyrosine phosphatase activity, Transmembrane receptor protein phosphatase activity, and cyclohydrolase activity (Fig. 3, Table 2 and 3).
Hub proteins participated in the astrocyte and oligodendrocyte derived ALS.
In this part of the study, a more in-depth analysis of relationship between proteins with genes associated astrocyte and oligodendrocyte derived ALS was performed. KRAS, GSK, IRS1, PLCH1, AKR1C3, and IPMK in astrocyte and oligodendrocyte derived ALS were observed. TP53, MDM2, GADD45A, PKH, GAPDH, and LDHA participated in astrocyte derived ALS and PTPRC, PTK2, MLLT4, ACADS, FZD1, and ACSM2B prominent role oligodendrocyte derived ALS (Fig. 4). For more details visit the figures S1, S2, S3.
Candidate critical miRNAs and extracellular vesicles’ miRNAs in regulating astrocyte and oligodendrocyte derived ALS.
In this part of the study, uploaded the genes involved in astrocyte and oligodendrocyte derived ALS to the MienTurnet database. hsa-miR-4280-3p, hsa-miR-428-5p, hsa-miR-1225-3p, hsa-miR-323b-5p, hsa-miR-184-3p, hsa-miR-423-3p, hsa-miR-515-5p, hsa-miR-3559-5p, and hsa-miR-4746-3p were selected as the most important linkages with hub genes and proteins products (Fig. 5). Also showed the relationships of the other miRNAs that were significant in the miRnet database as a communication network. Then to examine the miRNAs in the extracellular vesicles, the miR-658-3p, hsa-miR-564, hsa-miR-496-5p, hsa-miR-324-5p, hsa-miR-296-5p, and hsa-miR-4258-3p were more pronounced in astrocyte and oligodendrocyte derived ALS. Also hsa-miR-1244-3p, hsa-miR-409-3p, hsa-miR-496-3p, hsa-miR-658-3p, hsa-miR-423-3p, and hsa-miR-3146-3p were observed in miRnome ALS and extracellular vesicles (Fig. 6).